ω-Aryl-inter-phenylene-12,13(e)-didehydro-13,14-dihydro-PGD1 compounds

ABSTRACT

Prostaglandin analogs with the following cyclopentane ring structure: ##STR1## are disclosed along with intermediates useful in their preparation and processes for their preparation. These analogs are useful for some of the same pharmacological purposes as the prostaglandins, particularly and especially as blood platelet aggregation inhibitors.

The present application is a divisional application of Ser. No. 809,249,filed June 23, 1977, now U.S. Pat. No. 4,142,052 issued Feb. 27, 1979;which is a divisional application of Ser. No. 614,244, filed Sept. 17,1975, now pending. Likewise, U.S. Ser. No. 809,248, filed June 23, 1977,now U.S. Pat. No. 4,099,014 issued on July 4, 1978, is a divisionalapplication of Ser. No. 614,244.

The present invention relates to prostaglandin analogs for which theessential material constituting a disclosure therefor is incorporated byreference here from U.S. Pat. No. 4,099,014.

1. A prostaglandin analog of the formula ##STR2## WHEREIN D is ##STR3##wherein Y is ═CH--CH₂ --; wherein Z₆ is ##STR4## WHEREIN G IS ONE, 2, OR3; WHEREIN M₁ is ##STR5## wherein R₅ and R₆ are hydrogen or methyl, withthe proviso that one of R₅ and R₆ is methyl only when the other ishydrogen;Wherein L₁ is ##STR6## or a mixture of ##STR7## wherein R₃ andR₄ are hydrogen, methyl, or fluoro, being the same or different, withthe proviso that one of R₃ and R₄ is hydrogen or fluoro only when theother is hydrogen or fluoro; Wherein Z₃ is oxa or methylene; Wherein Tis chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms,inclusive, or alkoxy of one to 3 carbon atoms, inclusive, and s is zero,one, 2, or 3, the various T's being the same or different, with theproviso that not more than two T's are other than alkyl, with thefurther proviso that Z₃ is oca only when R₃ and R₄ are hydrogen ormethyl, being the same or different; and R₁ is hydrogen, alkyl of one to12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms,inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenylsubstituted with one, two, or three chloro or alkyl of one to 3 carbonatoms, inclusive, or a pharmacologically acceptable cation.
 2. Acompound according to claim 1, wherein M₁ is ##STR8##
 3. A compoundaccording to claim 1, wherein M₁ is ##STR9##
 4. A compound according toclaim 3, wherein D is ##STR10##
 5. A compound according to claim 4,wherein Z₃ is methylene.
 6. A compound according to claim 5, wherein sis zero or one and T is chloro, fluoro, or trifluoromethyl.
 7. Acompound according to claim 6, wherein g is one.
 8. A compound accordingto claim 7, wherein R₅ and R₆ are both hydrogen.
 9. A compound accordingto claim 8, wherein R₃ and R₄ are both hydrogen. 10.3,7-Inter-m-phenylene-17-phenyl-4,5,6,18,19,20-hexanor-13,14-dihydro-12,13(E)-didehydro-9-deoxy-PGD₁,a compound according to claim
 9. 11. A compound according to claim 4,wherein Z₃ is oxa.
 12. A compound according to claim 11, wherein s iszero or one and T is chloro, fluoro, or trifluoromethyl.
 13. A compoundaccording to claim 12, wherein g is one.
 14. A compound according toclaim 1, wherein R₅ and R₆ are both hydrogen.
 15. A compound accordingto claim 14, wherein R₃ and R₄ are both hydrogen. 16.3,7-Inter-m-phenylene-4,5,6-trinor-16-phenoxy-17,18,19,20-tetranor-13,14-dihydro-12,13(E)-didehyro-9-deoxy-PGD₁,a compound according to claim
 15. 17. A compound according to claim 3,wherein D is ##STR11##
 18. A compound according to claim 17, wherein Z₃is methylene.
 19. A compound according to claim 18, wherein s is zero orone and T is chloro, fluoro, or trifluoromethyl.
 20. A compoundaccording to claim 19, wherein g is one.
 21. A compound according toclaim 20, wherein R₅ and R₆ are both hydrogen.
 22. A compound accordingto claim 21, wherein R₃ and R₄ are both hydrogen. 23.3,7-Inter-m-phenylene-17-phenyl-2,3,4,17,18,19,20-heptanor-12,13(E)-didehydro-13,14-dihydro-9,10-didehydro-9-deoxy-PGD₁,a compound according to claim
 22. 24. A compound according to claim 17,wherein Z₃ is oxa.
 25. A compound according to claim 24, wherein s iszero or one and T is chloro, fluoro, or trifluoromethyl.
 26. A compoundaccording to claim 25, wherein g is one.
 27. A compound according toclaim 26, wherein R₅ and R₆ are both hydrogen.
 28. A compound accordingto claim 27, wherein R₃ and R₄ are both hydrogen. 29.3,7-Inter-m-phenylene-16-phenoxy-4,5,6,17,18,19,20-heptanor-12,13(E)-didehydro-13,14-dihydro-9,10-didehydro-9-deoxy-PGD₁,a compound according to claim
 28. 30. A compound according to claim 3,wherein D is ##STR12##
 31. A compound according to claim 30, wherein Z₃is methylene.
 32. A compound according to claim 31, wherein s is zero orone and T is chloro, fluoro, or trifluoromethyl.
 33. A compoundaccording to claim 32, wherein g is one.
 34. A compound according toclaim 33, wherein R₅ and R₆ are both hydrogen.
 35. A compound accordingto claim 34, wherein R₃ and R₄ are both hydrogen. 36.3,7-Inter-m-phenylene-17-phenyl-4,5,6,18,19,20-hexanor-12,13(E)-didehydro-13,14-dihydro-9β-PGD₁,a compound according to claim
 35. 37. A compound according to claim 30,wherein Z₃ is oxa.
 38. A compound according to claim 37, wherein s iszero or one and T is chloro, fluoro, or trifluoromethyl.
 39. A compoundaccording to claim 38, wherein g is one.
 40. A compound according toclaim 39, wherein R₅ and R₆ are both hydrogen.
 41. A compound accordingto claim 40, wherein R₃ and R₄ are both hydrogen. 42.3,7-Inter-m-phenylene-16-phenoxy-4,5,6,18,19,20-heptanor-12,13(E)-didehydro-13,14,-dihydro-9β-PGD₁,a compound according to claim
 41. 43. A compound according to claim 3,wherein D is ##STR13##
 44. A compound according to claim 43, wherein Z₃is methylene.
 45. A compound according to claim 44, wherein s is zero orone and T is chloro, fluoro, or trifluoromethyl.
 46. A compoundaccording to claim 45, wherein g is one.
 47. A compound according toclaim 46, wherein R₅ and R₆ are both hydrogen.
 48. A compound accordingto claim 47, wherein R₃ and R₄ are both hydrogen. 49.3,7-Inter-m-phenylene-17-phenyl-4,5,6,18,19,20-hexanor-12,13(E)-didehydro-13,14-dihydro-PGD₁,a compound according to claim
 48. 50. A compound according to claim 43,wherein Z₃ is oxa.
 51. A compound according to claim 50, wherein s iszero or one and T is chloro, fluoro, or trifluoromethyl.
 52. A compoundaccording to claim 51, wherein g is one.
 53. A compound according toclaim 52, wherein R₅ and R₆ are both hydrogen.
 54. A compound accordingto claim 53, wherein R₃ and R₄ are both hydrogen. 55.3,7-Inter-m-phenylene-16-phenoxy-4,5,6,17,18,19,20-heptanor-12,13(E)-didehydro-13,14-dihydro-PGD₁,a compound according to claim 54.